This invention relates to a new chemoattractant receptor and its use. More particularly, this invention relates to cDNA encoding a novel heptahelix receptor widely distributed in brain and peripheral tissues. This invention also relates to the use of the receptor for detecting Burkitt""s lymphoma cells.
The G-protein coupled (heptahelix) membrane receptors (1) receive chemical signals in cell communication both in CNS and in the peripheral tissues. Interest has recently focused also on the immune system because this receptor type is recognized by many chemoattractant peptides, the model substances being IL8 (2,3), and heptahelix receptors are now recognized also among cluster determinant antigens in immune cells, i.e., CDw78 (4) and CD97 (5).
In addition, the G-protein coupled receptors may be involved in other functional mechanisms, such as viral pathogenesis. Thus, the human cytomegalovirus shows structural homology with heptahelix receptors (6) and encodes a functional chemokine receptor (7), and Herpesvirus saimiri exerts xe2x80x9cmolecular piracyxe2x80x9d of the IL8B receptor (8). It has recently been shown that the entry of HIV-1 into CD4-positive cells is mediated by two distinct chemoattractant receptors (9-10). Herpesvirus saimiri is closely related to the B lymphotropic Epstein-Barr virus (EBV). This is implicated in several human malignancies, such as Burkitt""s lymphoma, which expresses BLR1, the first example of a heptahelix (chemokine-like) receptor identified specifically in the lymphocyte lineage of the hematopoietic system (11).
Because of the continuing interest in chemoattractant receptors, there exists a need in the art for the identification of new receptors and the elucidation of their structure so that the function of these receptors in humans can be determined. In particular, there exists a need in the art for sequence information on such receptors, including DNA and amino acid sequences, to enable the isolation and characterization of particular receptors as well as structurally related receptors. The identification of receptors associated with pathogenic conditions would be particularly advantageous in assays for the identification of these conditions in susceptible individuals.
Accordingly, this invention aids in fulfilling these needs in the art. More particularly, this invention provides a B-cell derived heptahelix receptor that is strongly expressed in brain and peripheral tissues. The receptor can be detected in Burkitt""s lymphoma cells. A receptor of human origin shows structural identity with both the IL8 receptors and with the co-receptors for HIV-1.
More particularly, the present invention provides isolated heptahelix receptors and DNA sequences encoding these heptahelix receptors. Such DNA sequences include (a) cDNA clones having a nucleotide sequence derived from the coding region of a native heptahelix receptor gene of the invention; (b) DNA sequences that are capable of hybridization to the cDNA clones of (a) under moderately stringent conditions and which encode biologically active heptahelix receptor molecules; and (c) DNA sequences that are degenerate as a result of the genetic code to the DNA sequences defined in (a) and (b) and which encode biologically active heptahelix receptor molecules.
The present invention also provides recombinant expression vectors comprising the DNA sequences defined above, recombinant heptahelix receptor molecules produced using the recombinant expression vectors, and processes for producing the recombinant heptahelix receptor molecules using the expression vectors.
The present invention further provides isolated or purified protein compositions comprising heptahelix receptor of the invention.
In one embodiment of the invention, a heptahelix receptor of the invention has the following amino acid sequence and corresponding nucleotide sequence:
The heptahelix receptor compositions of the invention are useful in diagnostic assays for heptahelix receptor, as well as in raising antibodies to heptahelix receptor for use in diagnosis and therapy. In addition, the heptahelix receptor compositions can be used directly in therapy to bind or scavenge chemoat-tractants, thereby providing a means for regulating the immune activities of chemoattractants. In particular, because the heptahelix receptor of the invention is expressed in Burkitt""s lymphoma, the invention is useful for detecting these lymphoma cells, for example, by immunoassay for heptahelix polypeptides of the invention or by detection of all or part of the polynucleotides encoding the receptor of the invention, such as by hybridization assays or amplification reactions.